Parra Alicia Lagarto, Rodriguez Julio Cesar Garcia
Drug Research and Development Center. CIDEM. Habana, Cuba.
Cent Nerv Syst Agents Med Chem. 2012 Mar;12(1):60-8. doi: 10.2174/187152412800229143.
The most common cause of stroke is cerebral ischemia, where blood flow to the brain is interrupted due to a thrombus in a major cerebral artery. Currently, the only therapeutic approach available is thrombolysis. A more recent approach that has started to gain attention is neuroprotection, the ability to prevent neuronal death and enhance endogenous protective mechanisms. Several studies have shown the neuroprotective action of Erythropoietin (EPO). A potential problem in the use of EPO for neurodegenerative disorders is the undesirable erythropoietic side effects. In this context, investigations have been focused to develop derivatives of EPO lacking erythropoietic activity but retaining neuroprotective potential. Low sialic acid-containing EPO (Neuro EPO) is very similar to the one that occurs in the mammalian brain and is rapidly degraded by the liver. Similar neuroprotective effects had been observed with neuro EPO, original recombinant human EPO and EPO variants in ischemia models. Intranasal route could be safe and hematological side effects could be avoided. Neuro EPO that constitutes a new agent has retained the neuroprotective effects without stimulating the EPOR in the bone marrow and can therefore be used without increasing the hematocrit. This review gives a brief introduction to the no hematopoietic effects of EPO, the evidence of neuroprotective effect, the alternatives for obtaining an EPO derivate without hematological side effects and discusses the advantages of nasal administration of Neuro EPO for neuroprotective stroke treatment.
中风最常见的病因是脑缺血，即由于大脑主要动脉中的血栓导致脑部血流中断。目前，唯一可用的治疗方法是溶栓治疗。最近开始受到关注的一种方法是神经保护，即预防神经元死亡并增强内源性保护机制的能力。多项研究已表明促红细胞生成素（EPO）具有神经保护作用。在将EPO用于神经退行性疾病时，一个潜在问题是不良的促红细胞生成副作用。在此背景下，研究重点已转向开发缺乏促红细胞生成活性但保留神经保护潜力的EPO衍生物。低唾液酸含量的EPO（神经EPO）与哺乳动物大脑中存在的EPO非常相似，且会被肝脏迅速降解。在缺血模型中，神经EPO、原始重组人EPO和EPO变体均观察到了类似的神经保护作用。经鼻途径可能是安全的，并且可以避免血液学副作用。作为一种新药的神经EPO保留了神经保护作用，而不会刺激骨髓中的EPOR，因此可以在不增加血细胞比容的情况下使用。本文综述简要介绍了EPO的非造血作用、神经保护作用的证据、获得无血液学副作用的EPO衍生物的替代方法，并讨论了经鼻给药神经EPO用于神经保护中风治疗的优势。
